Factor Xa inhibitors versus vitamin K antagonists for preventing embolism in AF patients


Clinical question: Do factor Xa inhibitors reduce the incidence of strokes and systemic embolic events, compared with warfarin, in people with atrial fibrillation?

Background: Factor Xa inhibitors, called DOACs or direct-acting anticoagulants, and vitamin K antagonists (VKAs) are part of treatment guidelines for preventing stroke and systemic embolic events in people with atrial fibrillation (AF). This study assessed the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for preventing cerebral or systemic embolic events in AF.

Study design: Cochrane Review update.

Dr. Janeesh Veedu, division of hospital medicine, University of Kentucky, Lexington

Dr. Janeesh Veedu

Setting: Data obtained from trial registers of the Cochrane Central Register of Controlled Trials (August 2017), the Cochrane Heart Group and the Cochrane Stroke Group (September 2016), Embase (1980 to April 2017), and MEDLINE (1950 to April 2017). Authors also screened reference lists and contacted pharmaceutical companies, authors, and sponsors of relevant published trials.

Synopsis: The study included 42,084 participants from 10 trials with a diagnosis of AF who were eligible for long-term anticoagulation with warfarin (target INR 2-3).

The trials directly compared dose-adjusted warfarin with factor Xa inhibitors. Median follow-up ranged from 12 weeks to 1.9 years, and composite primary endpoint was all strokes (both ischemic and hemorrhagic) and non–central nervous systemic embolic events. Factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events, compared with dose-adjusted warfarin (odds ratio, 0.81; 95% confidence interval, 0.72-0.91), reduced the number of major bleeding events (OR, 0.92; 95% CI, 0.63-1.34), and significantly reduced the risk of intracranial hemorrhage (OR, 0.56; 95% CI, 0.45-0.70). They also significantly reduced the number of all-cause deaths (OR, 0.88; 95% CI, 0.81-0.97). One limitation of this study is the heterogeneity and hence lower quality of evidence. This study shows a small net clinical benefit of using factor Xa inhibitors in AF because of a reduction in strokes and systemic embolic events and also a lower risk of bleeding (including intracranial hemorrhages), compared with using warfarin.

Bottom line: Patients with AF have a lower incidence of strokes and systemic embolic events when treated with factor Xa inhibitors, compared with those treated with warfarin.

Citation: Bruins Slot KM et al. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. Cochrane Database Syst Rev. 2018 Mar 6. doi: 10.1002/14651858.CD008980.pub3.

Dr. Veedu is a hospitalist and instructor in the division of hospital medicine at the University of Kentucky, Lexington.

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